{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T21:16:24Z","timestamp":1789766184766,"version":"4.0.1"},"reference-count":82,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2021,10,12]],"date-time":"2021-10-12T00:00:00Z","timestamp":1633996800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006261","name":"Taif University","doi-asserted-by":"publisher","award":["TURSP-2020\/131"],"award-info":[{"award-number":["TURSP-2020\/131"]}],"id":[{"id":"10.13039\/501100006261","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Irisin is a clinically significant protein playing a valuable role in regulating various diseases. Irisin attenuates synaptic and memory dysfunction, highlighting its importance in Alzheimer\u2019s disease. On the other hand, Microtubule Affinity Regulating Kinase 4 (MARK4) is associated with various cancer types, uncontrolled neuronal migrations, and disrupted microtubule dynamics. In addition, MARK4 has been explored as a potential drug target for cancer and Alzheimer\u2019s disease therapy. Here, we studied the binding and subsequent inhibition of MARK4 by irisin. Irisin binds to MARK4 with an admirable affinity (K = 0.8 \u00d7 107 M\u22121), subsequently inhibiting its activity (IC50 = 2.71 \u00b5m). In vitro studies were further validated by docking and simulations. Molecular docking revealed several hydrogen bonds between irisin and MARK4, including critical residues, Lys38, Val40, and Ser134. Furthermore, the molecular dynamic simulation showed that the binding of irisin resulted in enhanced stability of MARK4. This study provides a rationale to use irisin as a therapeutic agent to treat MARK4-associated diseases.<\/jats:p>","DOI":"10.3390\/ijms222010986","type":"journal-article","created":{"date-parts":[[2021,10,12]],"date-time":"2021-10-12T17:29:18Z","timestamp":1634059758000},"page":"10986","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["MAP\/Microtubule Affinity Regulating Kinase 4 Inhibitory Potential of Irisin: A New Therapeutic Strategy to Combat Cancer and Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"22","author":[{"given":"Rashid","family":"Waseem","sequence":"first","affiliation":[{"name":"Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saleha","family":"Anwar","sequence":"additional","affiliation":[{"name":"Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shama","family":"Khan","sequence":"additional","affiliation":[{"name":"Drug Discovery and Development Centre (H3D), University of Cape Town, Rondebosch 7701, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7055-7056","authenticated-orcid":false,"given":"Anas","family":"Shamsi","sequence":"additional","affiliation":[{"name":"Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3663-4940","authenticated-orcid":false,"given":"Md. Imtaiyaz","family":"Hassan","sequence":"additional","affiliation":[{"name":"Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8597-6015","authenticated-orcid":false,"given":"Farah","family":"Anjum","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7116-3611","authenticated-orcid":false,"given":"Alaa","family":"Shafie","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9060-7970","authenticated-orcid":false,"given":"Asimul","family":"Islam","sequence":"additional","affiliation":[{"name":"Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1102-1993","authenticated-orcid":false,"given":"Dharmendra Kumar","family":"Yadav","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Gachon University of Medicine and Science, Hambakmoeiro, Yeonsu-gu, Incheon City 21924, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1038\/nature10777","article-title":"A PGC1-\u03b1-dependent myokine that drives brown-fat-like development of white fat and thermogenesis","volume":"481","author":"Wu","year":"2012","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1016\/j.cmet.2015.08.001","article-title":"Detection and quantitation of circulating human irisin by tandem mass spectrometry","volume":"22","author":"Jedrychowski","year":"2015","journal-title":"Cell Metab."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"7910","DOI":"10.1021\/acsomega.1c00517","article-title":"Multispectroscopic and Molecular Docking Insight into Elucidating the Interaction of Irisin with Rivastigmine Tartrate: A Combinational Therapy Approach to Fight Alzheimer\u2019s Disease","volume":"6","author":"Waseem","year":"2021","journal-title":"ACS Omega"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.bbrc.2016.04.047","article-title":"Irisin ameliorates depressive-like behaviors in rats by regulating energy metabolism","volume":"474","author":"Wang","year":"2016","journal-title":"Biochem. 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